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ObjectiveTo estimate the risk of Long COVID by socioeconomic deprivation and to further examine the socioeconomic inequalities in Long COVID by sex and occupational groups. DesignWe analysed data from the COVID-19 Infection Survey conducted by the Office for National Statistics between 26/04/2020 and 31/01/2022. This is the largest and nationally representative survey of COVID-19 in the UK and provides uniquely rich, contemporaneous, and longitudinal data on occupation, health status, COVID-19 exposure, and Long COVID symptoms. SettingCommunity-based longitudinal survey of COVID-19 in the UK. ParticipantsWe included 201,799 participants in our analysis who were aged between 16 and 64 years and had a confirmed SARS-CoV-2 infection. Main outcome measuresWe used multivariable logistic regression models to estimate the risk of Long COVID at least 4 weeks after acute SARS-CoV-2 infection by deciles of index of multiple deprivation (IMD) and adjusted for a range of demographic and spatiotemporal factors. We further examined the modifying effects of socioeconomic deprivation by sex and occupational groups. ResultsA total of 19,315 (9.6%) participants reported having Long COVID symptoms. Compared to the least deprived IMD decile, participants in the most deprived decile had a higher adjusted risk of Long COVID (11.4% vs 8.2%; adjusted OR: 1.45; 95% confidence interval [CI]: 1.33, 1.57). There were particularly significantly higher inequalities (most vs least deprived decile) of Long COVID in healthcare and patient facing roles (aOR: 1.76; 1.27, 2.44), and in the education sector (aOR: 1.62; 1.26, 2.08). The inequality of Long COVID was higher in females (aOR: 1.54; 1.38, 1.71) than males (OR: 1.32; 1.15, 1.51). ConclusionsParticipants living in the most socioeconomically deprived areas had a higher risk of Long COVID. The inequality gap was wider in females and certain public facing occupations (e.g., healthcare and education). These findings will help inform public health policies and interventions in adopting a social justice and health inequality lens.
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BackgroundAlthough morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described. MethodsAnalyses used national administrative electronic hospital records in England, Scotland and Wales for 2016-2021. Admissions and procedures during the pandemic (2020-2021) related to six major cardiovascular conditions (acute coronary syndrome, heart failure, stroke/transient ischaemic attack, peripheral arterial disease, aortic aneurysm, and venous thromboembolism) were compared to the annual average in the pre-pandemic period (2016-2019). Differences were assessed by time period and urgency of care. ResultsIn 2020, there were 31,064 (-6%) fewer hospital admissions (14,506 [-4%] fewer emergencies, 16,560 [-23%] fewer elective admissions) compared to 2016-2019 for the six major cardiovascular diseases combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries (-10,996 [-15%] fewer admissions). However, these reductions were offset by higher than expected total emergency admissions (+25,878 [+6%] higher admissions), notably for heart failure and stroke in England, and for venous thromboembolism in all three countries. Analyses for procedures showed similar temporal variations to admissions. ConclusionThis study highlights increasing emergency cardiovascular admissions as a result of the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years. Key QuestionWhat is the impact in 2020 and 2021 of the COVID-19 pandemic on hospital admissions and procedures for six major cardiovascular diseases in England, Scotland and Wales? Key FindingIn 2020, there were 6% fewer hospital admissions (emergency: -4%, elective: -23%) compared to 2016-2019 for six major cardiovascular diseases, across three UK countries. Overall, admissions returned to pre-pandemic levels in 2021, but elective admissions remained below expected levels. Take-home MessageThere was increasing emergency cardiovascular admissions as a result of the pandemic, with substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.
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Background and aimLong Covid is a significant public health concern with potentially negative implications for health inequalities. We know that those who are already socially disadvantaged in society are more exposed to COVID-19, experience the worst health outcomes and are more likely to suffer economically. We also know that these groups are more likely to experience stigma and discrimination and have negative healthcare experiences even before the pandemic. However, little is known about disadvantaged groups experiences of Long Covid and preliminary evidence suggests they may be under-represented in those who access formal care. We will conduct a pilot study in a defined geographical area (Camden, London, UK) to test the feasibility of a community-based approach of identifying Long Covid cases that have not been formally clinically diagnosed and have not been referred to Long Covid Specialist services. We will explore the barriers to accessing recognition, care and support, as well as experiences of stigma and perceived discrimination. MethodsThis protocol and study materials were co-produced with a Community Advisory Board (CAB) made up primarily of people living with Long Covid. Working with voluntary organisations, promotional material are co-developed and will be distributed in the local community with engagement from key community organisations and leaders to highlight Long Covid symptoms and invite those experiencing them to participate in the study if they are not formally diagnosed and accessing care. Awareness of Long Covid and symptoms, experiences of trying to access care, as well as stigma and discrimination will be explored through qualitative interviews with participants. Upon completion of the interviews, participants will be offered referral to the local social prescribing team to receive support that is personalised to them potentially including, but not restricted to, liaising with their primary care provider and the regional Long Covid clinic run by University College London Hospitals (UCLH). Ethics and disseminationEthical approval has been obtained from the Faculty of Medicine Ethics Committee and Research Integrity and Governance, University of Southampton. (reference number 72400). Findings will be reported in a report and submitted for peer-reviewed publication. Definitive methods of dissemination will be decided by the CAB. Summaries of the findings will also be shared on the STIMULATE-ICP website, locally in the study area and through social media. We will specifically target policy makers and those responsible for shaping and commissioning Long Covid healthcare services and social support such as NHSE England Long Covid Group.
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IntroductionLong COVID (LC), the persistent symptoms [≥]12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway (ICP) approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace. Methods and analysisThis is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an ICP (Coverscan, a multi-organ MRI, and Living with COVID Recovery, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that ICP interventions are delivered as "standard of care" in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 NHS LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes (e.g. EQ-5D-5L, GAD-7, PHQ-9, WSAS, PDQ-5, CFQ, SF-12, MRC Dyspnoea score) at 3 months. The trial also includes an economic evaluation which will be described separately. Ethics and disseminationThe protocol was reviewed by South Central - Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan has UKCA certification (752965). The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations. Trial registration numberISRCTN10665760
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ObjectivesTo evaluate implementation of EHR-integrated NEWS2 in a cardiac care setting and a general hospital setting in the COVID-19 pandemic. DesignThematic analysis of qualitative semi-structured interviews with purposefully sampled nurses and managers, as well as online surveys. SettingsSpecialist cardiac hospital (St Bartholomews Hospital) and General teaching hospital (University College London Hospital). ParticipantsEleven nurses and managers from cardiology, cardiac surgery, oncology, and intensive care wards (St Bartholomews) and medical, haematology and intensive care wards (UCLH) were interviewed and sixty-seven were surveyed online. ResultsThree main themes emerged: (i) Implementing NEWS2 challenges and supports; (ii) Value of NEWS2 to alarm, escalate, particularly during the pandemic; and (iii) Digitalisation: EHR integration and automation. The value of NEWS2 was partly positive in escalation, yet there were concerns by nurses who undervalued NEWS2 particularly in cardiac care. Challenges, like clinicians behaviours, lack of resources and training and the perception of NEWS2 value, limit the success of this implementation. Changes in guidelines in the pandemic have led to overlooking NEWS2. EHR integration and automated monitoring are improvement solutions that are not fully employed yet. ConclusionWhether in specialist or general medical settings, the health professionals implementing EWS in healthcare face cultural and systems related challenges to adopting NEWS2 and digital solutions. The validity of NEWS2 in specialised settings and complex conditions is not yet apparent and requires comprehensive validation. EHRs integration and automation are powerful tools to facilitate NEWS2 if its principles are reviewed and rectified, and resources and training are accessible. Further examination of implementation from the cultural and automation domains are needed.
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IntroductionIndividuals with Long Covid represent a new and growing patient population. In England, fewer than 90 Long Covid clinics deliver assessment and treatment informed by NICE guidelines. However, a paucity of clinical trials or longitudinal cohort studies means that the epidemiology, clinical trajectory, healthcare utilisation and effectiveness of current Long Covid care are poorly documented, and that neither evidence-based treatments nor rehabilitation strategies exist. In addition, and in part due to pre-pandemic health inequalities, access to referral and care varies, and patient experience of the Long Covid care pathways can be poor. In a mixed methods study, we therefore aim to: (1) describe the usual healthcare, outcomes and resource utilisation of individuals with Long Covid; (2) assess the extent of inequalities in access to Long Covid care, and specifically to understand Long Covid patients experiences of stigma and discrimination. Methods and analysisA mixed methods study will address our aims. Qualitative data collection from patients and health professionals will be achieved through surveys, interviews and focus group discussions, to understand their experience and document the function of clinics. A patient cohort study will provide an understanding of outcomes and costs of care. Accessible data will be further analysed to understand the nature of Long Covid, and the care received. Ethics and disseminationEthical approval was obtained from South Central - Berkshire Research Ethics Committee (reference 303958). The dissemination plan will be decided by the patient and public involvement and engagement (PPIE) group members and study Co-Is, but will target 1) policy makers, and those responsible for commissioning and delivering Long Covid services, 2) patients and the public, and 3) academics.
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IntroductionAs mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in delivering care for patients with multi-morbidity. The multi-system nature of Long COVID and its impact on physical and psychological health demands a more effective model of holistic, integrated care. The evolution of integrated care systems (ICSs) in the UK presents an important opportunity to explore areas of mutual benefit to LTC, multi-morbidity and Long COVID care. There may be benefits in comparing and contrasting ICPs for Long COVID with ICPs for other LTCs. Methods and analysisThis study aims to evaluate health services requirements for ICPs for Long COVID and their applicability to other LTCs including multi-morbidity and the overlap with medically not yet explained symptoms (MNYES). The study will follow a Delphi design and involve an expert panel of stakeholders including people with lived experience, as well as clinicians with expertise in Long COVID and other LTCs. Study processes will include expert panel and moderator panel meetings, surveys, and interviews. The Delphi process is part of the overall STIMULATE-ICP programme, aimed at improving integrated care for people with Long COVID. Ethics and disseminationEthical approval for this Delphi study has been obtained (Research Governance Board of the University of York) as have approvals for the other STIMULATE-ICP studies. Study outcomes are likely to inform policy for ICPs across LTCs. Results will be disseminated through scientific publication, conference presentation and communications with patients and stakeholders involved in care of other LTCs and Long COVID. RegistrationResearchregistry: https://www.researchregistry.com/browse-the-registry#home/registrationdetails/6246bfeeeaaed6001f08dadc/.
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BackgroundLong Covid is associated with multiple symptoms and impairment in multiple organs. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiac magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid. Methods534 individuals with Long Covid underwent baseline CMR (T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms and 330 were rescanned at 12.6 (IQR 11.4, 14.2) months if abnormal findings were reported at baseline. Symptoms, standardised questionnaires, and blood samples were collected at both timepoints. Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in [≥]3 cardiac segments. A significant change over time was reported by comparison with 92 healthy controls. ResultsThe technical success of this multiorgan assessment in non-acute settings was 99.1% at baseline, and 98.3% at follow up, with 99.6% and 98.8% for CMR respectively. Of individuals with Long Covid, 102/534 [19%] had cardiac impairment at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and low GLS were associated with cardiac impairment. Low LVEF at baseline was associated with persistent cardiac impairment at 12 months. ConclusionCardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options.
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ObjectivesTo assess whether there is a change in the incidence of cardiac and all-cause death in young people following COVID-19 vaccination or SARS-CoV-2 infection in unvaccinated individuals. DesignSelf-controlled case series. SettingNational, linked electronic health record data in England. Study populationIndividuals aged 12-29 who had received at least one dose of COVID-19 vaccination and died between 8 December 2020 and 2 February 2022 and registered by 16 February 2022 within 12 weeks of COVID-19 vaccination; Individuals aged 12-29 who died within 12 weeks of testing positive for SARS-CoV-2. Main outcome measuresCardiac and all-cause deaths occurring within 12 weeks of vaccination or SARS-CoV-2 infection. ResultsCompared to the baseline period, there was no evidence of a change in the incidence of cardiac death in the six weeks after vaccination, whether for each of weeks 1 to 6 or the whole six-week period. There was a decrease in the risk of all-cause death in the first week after vaccination and no change in each of weeks 2 to 6 after vaccination or whole six-week period after vaccination. Subgroup analyses by sex, age, vaccine type, and last dose also showed no change in the risk of death in the first six weeks after vaccination. There was a large increase in the incidence of cardiac and all-cause death in the overall risk period after SARS-CoV-2 infection among the unvaccinated. ConclusionThere is no evidence of an association between COVID-19 vaccination and an increased risk of death in young people. By contrast, SARS-CoV-2 infection was associated with substantially higher risk of cardiac related death and all-cause death. What is already known on this topicSeveral studies have highlighted the association between COVID-19 vaccination and the risk of myocarditis, myopericarditis, and other cardiac problems, especially in young people, but associated risk of mortality is unclear. Since younger people have lower risk of COVID-19 hospitalisation and mortality, the mortality risk associated with vaccination is potentially more important to them in balancing the risk and benefit of vaccination. What this study addsAlthough there is a risk of myocarditis or myopericarditis with COVID-19, there is no evidence of increased risk of cardiac or all-cause mortality following COVID-19 vaccination in young people aged 12 to 29. Given the increased risk of mortality following SARS-CoV-2 infection in this group, the risk-benefit analysis favours COVID-19 vaccination for this age group.
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ImportanceMulti-organ impairment associated with Long COVID is a significant burden to individuals, populations and health systems, presenting challenges for diagnosis and care provision. Standardised assessment across multiple organs over time is lacking, particularly in non-hospitalised individuals. ObjectiveTo determine the prevalence of organ impairment in Long COVID patients at 6 and at 12 months after initial symptoms and to explore links to clinical presentation. DesignThis was a prospective, longitudinal study in individuals following recovery from acute COVID-19. We assessed symptoms, health status, and multi-organ tissue characterisation and function, using consensus definitions for single and multi-organ impairment. Physiological and biochemical investigations were performed at baseline on all individuals and those with organ impairment were reassessed, including multi-organ MRI, 6 months later. SettingTwo non-acute settings (Oxford and London). Participants536 individuals (mean 45 years, 73% female, 89% white, 32% healthcare workers, 13% acute COVID-19 hospitalisation) completed baseline assessment (median: 6 months post-COVID-19). 331 (62%) with organ impairment or incidental findings had follow up, with reduced symptom burden from baseline (median number of symptoms: 10 and 3, at 6 and 12 months). ExposureSARS-CoV-2 infection 6 months prior to first assessment. Main outcomePrevalence of single and multi-organ impairment at 6 and 12 months post-COVID-19. ResultsExtreme breathlessness (36% and 30%), cognitive dysfunction (50% and 38%) and poor health-related quality of life (EQ-5D-5L<0.7; 55% and 45%) were common at 6 and 12 months, and associated with female gender, younger age and single organ impairment. At baseline, there was fibro-inflammation in the heart (9%), pancreas (9%), kidney (15%) and liver (11%); increased volume in liver (7%), spleen (8%) and kidney (9%); decreased capacity in lungs (2%); and excessive fat deposition in the liver (25%) and pancreas (15%). Single and multi-organ impairment were present in 59% and 23% at baseline, persisting in 59% and 27% at follow-up. Conclusion and RelevanceOrgan impairment was present in 59% of individuals at 6 months post-COVID-19, persisting in 59% of those followed up at 1 year, with implications for symptoms, quality of life and longer-term health, signalling need for prevention and integrated care of Long COVID. Trial RegistrationClinicalTrials.gov Identifier: NCT04369807 Key pointsO_LIQuestion: What is the prevalence of organ impairment in Long COVID at 6- and 12-months post-COVID-19? C_LIO_LIFindings: In a prospective study of 536 mainly non-hospitalised individuals, symptom burden decreased, but single organ impairment persisted in 59% at 12 months post-COVID-19. C_LIO_LIMeaning: Organ impairment in Long COVID has implications for symptoms, quality of life and longer-term health, signalling need for prevention and integrated care of Long COVID. C_LI
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ObjectiveTo assess the risk of death involving COVID-19 following infection from Omicron (B.1.1.539/BA.1) relative to Delta (B.1.617.2). DesignRetrospective cohort study. SettingEngland, UK, 1 December 2021 to 25 January 2022. Participants1,035,163 people aged 18-100 years who tested positive for SARS-CoV-2 in the national surveillance programme, and had an infection identified as either Omicron- or Delta compatible. Main outcome measuresDeath involving COVID-19 as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause-specific Cox proportional hazard regression models were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, Index of Multiple Deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Additionally, we tested for interactions between variant and sex, age, vaccination status and comorbidities. ResultsThe risk of death involving COVID-19 was 67% lower for Omicron compared to Delta and the reduction in the risk of death involving COVID-19 for Omicron compared to Delta was more pronounced in males than in females and in people under 70 years old than in people aged 70 years or over. Regardless of age, reduction of the risk of death from Omicron relative to Delta more was more pronounced in people who had received a booster than in those having received only two doses. ConclusionsOur results support early work showing the relative reduction in severity of Omicron compared to Delta in terms of hospitalisation and extends this research to assess COVID-19 mortality. Our work also highlights the importance of the vaccination booster campaign, where the reduction in risk of death involving COVID-19 is most pronounced in individuals who had received a booster. What is already known on this topicThe Omicron variant, which refers to the whole lineage (BA.1, BA.2, BA.3) had already been shown to be more transmissible than the Delta variant, but there is emerging evidence suggests that the risk of hospitalisation and risk of death within 28 days after a SARS-COV-2 test is lower. However, with a highly transmissible infection and high levels of population testing, definition of death within 28 days is more likely to be susceptible to misclassification bias due to asymptomatic or co-incidental infection. There is no study so far comparing the risk of COVID-19 death as identified from death certification records, with the cause of death assessed by the physician who attended the patient in the last illness. What this study addsUsing data from a large cohort of COVID-19 infections that occurred in December 2021, we examined the difference in the risk COVID-19 death, as identified from death certification records, between the Delta and Omicron BA.1 variant. Our study shows that risk of death involving COVID-19 was reduced by 67% following infection with the Omicron BA.1 variant relative to the Delta variant after adjusting for a wide range of potential confounders, including vaccination status and comorbidities. Importantly, we found that the relative risk of COVID-19 mortality following Omicron versus Delta infection varied by age and sex, with lower relative risk in younger individuals and for males than females. The reduction in risk of death involving COVID-19 was also most pronounced in individuals who had received a booster.
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ObjectivesTo estimate the impact of the COVID-19 pandemic on cardiovascular disease (CVD) and CVD management using routinely collected medication data as a proxy. DesignDescriptive and interrupted time series analysis using anonymised individual-level population-scale data for 1.32 billion records of dispensed CVD medications across 15.8 million individuals in England, Scotland and Wales. SettingCommunity dispensed CVD medications with 100% coverage from England, Scotland and Wales, plus primary care prescribed CVD medications from England (including 98% English general practices). Participants15.8 million individuals aged 18+ years alive on 1st April 2018 dispensed at least one CVD medicine in a year from England, Scotland and Wales. Main outcome measuresMonthly counts, percent annual change (1st April 2018 to 31st July 2021) and annual rates (1st March 2018 to 28th February 2021) of medicines dispensed by CVD/ CVD risk factor; prevalent and incident use. ResultsYear-on-year change in dispensed CVD medicines by month were observed, with notable uplifts ahead of the first (11.8% higher in March 2020) but not subsequent national lockdowns. Using hypertension as one example of the indirect impact of the pandemic, we observed 491,203 fewer individuals initiated antihypertensive treatment across England, Scotland and Wales during the period March 2020 to end May 2021 than would have been expected compared to 2019. We estimated that this missed antihypertension treatment could result in 13,659 additional CVD events should individuals remain untreated, including 2,281 additional myocardial infarctions (MIs) and 3,474 additional strokes. Incident use of lipid-lowering medicines decreased by an average 14,793 per month in early 2021 compared with the equivalent months prior to the pandemic in 2019. In contrast, the use of incident medicines to treat type-2 diabetes (T2DM) increased by approximately 1,642 patients per month. ConclusionsManagement of key CVD risk factors as proxied by incident use of CVD medicines has not returned to pre-pandemic levels in the UK. Novel methods to identify and treat individuals who have missed treatment are urgently required to avoid large numbers of additional future CVD events, further adding indirect cost of the COVID-19 pandemic.
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BackgroundUpdatable understanding of the onset and progression of individuals COVID-19 trajectories underpins pandemic mitigation efforts. In order to identify and characterize individual trajectories, we defined and validated ten COVID-19 phenotypes from linked electronic health records (EHR) on a nationwide scale using an extensible framework. MethodsCohort study of 56.6 million people in England alive on 23/01/2020, followed until 31/05/2021, using eight linked national datasets spanning COVID-19 testing, vaccination, primary & secondary care and death registrations data. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity using a combination of international clinical terminologies (e.g. SNOMED-CT, ICD-10) and bespoke data fields; positive test, primary care diagnosis, hospitalisation, critical care (four phenotypes), and death (three phenotypes). Using these phenotypes, we constructed patient trajectories illustrating the transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FindingsWe identified 3,469,528 infected individuals (6.1%) with 8,825,738 recorded COVID-19 phenotypes. Of these, 364,260 (11%) were hospitalised and 140,908 (4%) died. Of those hospitalised, 38,072 (10%) were admitted to intensive care (ICU), 54,026 (15%) received non-invasive ventilation and 21,404 (6%) invasive ventilation. Amongst hospitalised patients, first wave mortality (30%) was higher than the second (23%) in non-ICU settings, but remained unchanged for ICU patients. The highest mortality was for patients receiving critical care outside of ICU in wave 1 (51%). 13,083 (9%) COVID-19 related deaths occurred without diagnoses on the death certificate, but within 30 days of a positive test while 10,403 (7%) of cases were identified from mortality data alone with no prior phenotypes recorded. We observed longer patient trajectories in the second pandemic wave compared to the first. InterpretationOur analyses illustrate the wide spectrum of severity that COVID-19 displays and significant differences in incidence, survival and pathways across pandemic waves. We provide an adaptable framework to answer questions of clinical and policy relevance; new variant impact, booster dose efficacy and a way of maximising existing data to understand individuals progression through disease states. Research in ContextO_ST_ABSEvidence before the studyC_ST_ABSWe searched PubMed on October 14, 2021, for publications with the terms "COVID-19" or "SARS-CoV-2", "severity", and "electronic health records" or "EHR" without date or language restrictions. Multiple studies explore factors associated with severity of COVID-19 infection, and model predictions of outcome for hospitalised patients. However, most work to date focused on isolated facets of the healthcare system, such as primary or secondary care only, was conducted in subpopulations (e.g. hospitalised patients) of limited sample size, and often utilized dichotomised outcomes (e.g. mortality or hospitalisation) ignoring the full spectrum of disease. We identified no studies which comprehensively detailed severity of infections while describing disease severity across pandemic waves, vaccination status, and patient trajectories. Added value of this studyTo our knowledge, this is the first study providing a comprehensive view of COVID-19 across pandemic waves using national data and focusing on severity, vaccination, and patient trajectories. Drawing on linked electronic health record (EHR) data on a national scale (56.6 million people alive and registered with GP in England), we describe key demographic factors, frequency of comorbidities, impact of the two main waves in England, and effect of full vaccination on COVID-19 severities. Additionally, we identify and describe patient trajectory networks which illustrate the main transition pathways of COVID-19 patients in the healthcare system. Finally, we provide reproducible COVID-19 phenotyping algorithms reflecting clinically relevant stages of disease severity i.e. positive tests, primary care diagnoses, hospitalisation, critical care treatments (e.g. ventilatory support) and mortality. Implications of all the available evidenceThe COVID-19 phenotypes and trajectory analysis framework outlined produce a reproducible, extensible and repurposable means to generate national-scale data to support critical policy decision making. By modelling patient trajectories as a series of interactions with healthcare systems, and linking these to demographic and outcome data, we provide a means to identify and prioritise care pathways associated with adverse outcomes and highlight healthcare system touch points which may act as tangible targets for intervention.
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ObjectiveEvaluate antithrombotic (AT) use in individuals with atrial fibrillation (AF) and high stroke risk (CHA2DS2-VASc score>=2) and investigate whether pre-existing AT use may improve COVID-19 outcomes. MethodsIndividuals with AF and a CHA2DS2-VASc score>=2 on January 1st 2020 were identified using pseudonymised, linked electronic health records for 56 million people in England and followed-up until May 1st 2021. Factors associated with pre-existing AT use were analysed using logistic regression. Differences in COVID-19 related hospitalisation and death were analysed using logistic and Cox regression for individuals exposed to pre-existing AT use vs no AT use, anticoagulants (AC) vs antiplatelets (AP) and direct oral anticoagulants (DOACs) vs warfarin. ResultsFrom 972,971 individuals with AF and a CHA2DS2-VASc score>=2, 88.0% (n=856,336) had pre-existing AT use, 3.8% (n=37,418) had a COVID-19 related hospitalisation and 2.2% (n=21,116) died. Factors associated with no AT use included comorbidities that may contraindicate AT use (liver disease and history of falls) and demographics (socioeconomic status and ethnicity). Pre-existing AT use was associated with lower odds of death (OR=0.92 [0.87-0.96 at 95% CI]), but higher odds of hospitalisation OR=1.20 [1.15-1.26 at 95% CI]). The same pattern was observed for AC vs AP (death (OR=0.93 [0.87-0.98]), hospitalisation (OR=1.17 [1.11-1.24])) but not for DOACs vs warfarin (death (OR=1.00 [0.95-1.05]), hospitalisation (OR=0.86 [0.82-0.89]). ConclusionsPre-existing AT use may offer marginal protection against COVID-19 death, with AC offering more protection than AP. Although this association may not be causal, it provides further incentive to improve AT coverage for eligible individuals with AF. KEY QUESTIONSO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIAnticoagulants (AC), a sub-class of antithrombotics (AT), reduce the risk of stroke and are recommended for individuals with atrial fibrillation (AF) and at high risk of stroke (CHA2DS2-VASc score>=2, National Institute for Health and Care Excellence threshold). However, previous evaluations suggest that up to one third of these individuals may not be taking AC. Over estimation of bleeding and fall risk in elderly patients have been identified as potential factors in this under medicating. C_LIO_LIIn response to the COVID-19 pandemic, several observational studies have observed correlations between pre-existing AT use, particularly anticoagulants (AC), and lower risk of severe COVID-19 outcomes such as hospitalisation and death. However, these correlations are inconsistent across studies and have not compared all major sub-types of AT in one study. C_LI What does this study add?O_LIThis study uses datasets covering primary care, secondary care, pharmacy dispensing, death registrations, multiple COVID-19 diagnoses routes and vaccination records for 56 million people in England and is the largest scale evaluation of AT use to date. This provides the statistical power to robustly analyse targeted sub-types of AT and control for a wide range of potential confounders. All code developed for the study is opensource and an updated nationwide evaluation can be rapidly created for future time points. C_LIO_LIIn 972,971 individuals with AF and a CHA2DS2-VASc score>=2, we observed 88.0% (n=856,336) with pre-existing AT use which was associated with marginal protection against COVID-19 death (OR=0.92 [0.87-0.96 at 95% CI]). C_LI How might this impact on clinical practice?O_LIThese findings can help shape global AT medication policy and provide population-scale, observational analysis results alongside gold-standard randomised control trials to help assess whether a potential beneficial effect of pre-existing AT use on COVID-19 death alters risk to benefit assessments in AT prescribing decisions. C_LI
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ImportanceObesity and ethnicity are well characterised risk factors for severe COVID-19 outcomes, but the differential effects of obesity on COVID-19 outcomes by race/ethnicity has not been examined robustly in the general population. ObjectiveTo investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups. Design, Setting, and ParticipantsThis is a retrospective cohort study using linked national Census, electronic health records and mortality data for English adults aged 40 years or older who were alive at the start of pandemic (24th January 2020). ExposuresBMI obtained from electronic health records. Self-reported ethnicity (white, black, South Asian, other) was the effect-modifying variable. Main Outcomes and MeasuresCOVID-19 related death identified by ICD-10 codes U07.1 or U07.2 mentioned on the death certificate from 24th January 2020 until December 28th 2020. ResultsThe analysis included white (n = 11,074,708; mean age 61.9 [{+/-}13.4] years; 54% women), black (n = 416,542; 56.4 [{+/-}11.7] years; 57% women), South Asian (621,691; 55.7 [{+/-}12.4] years; 51% women) and other (n = 478,196; 55.3 [{+/-}11.6] years; 55% women) ethnicities with linked BMI data. The association between BMI and COVID-19 mortality was stronger in ethnic minority groups. Compared to a BMI of 22.5 kg/m2 in white ethnicities, the adjusted HR for COVID-19 mortality at a BMI of 30 kg/m2 in white, black, South Asian and other ethnicities was 0.95 (95% CI: 0.87-1.03), 1.72 (1.52-1.94), 2.00 (1.78-2.25) and 1.39 (1.21-1.61), respectively. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2 in white ethnicities (HR = 1.73) was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in black, South Asian and other ethnic groups, respectively. ConclusionsThis population-based study using linked Census and electronic health care records demonstrates that the risk of COVID-19 mortality associated with obesity is greater in ethnic minority groups compared to white populations. QuestionDoes the association between BMI and COVID-19 mortality vary by ethnicity? FindingsIn this study of 12.6 million adults, BMI was associated with COVID-19 in all ethnicities, but with stronger associations in ethnic minority populations such that the risk of COVID-19 mortality for a BMI of 40 kg/m2 in white ethnicities was observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in black, South Asian and other ethnicities, respectively. MeaningBMI is a stronger risk factor for COVID-19 mortality in ethnic minorities. Obesity management is therefore a priority in these populations.
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BackgroundComplications following SARS-CoV-2 infection require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated Post-COVID clinical service to include both hospitalised and non-hospitalised patients. MethodsIn a single-centre, observational analysis, we report outcomes for 1325 individuals assessed in the University College London Hospitals NHS Foundation Trust Post-COVID service between April 2020 and April 2021. Demography, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation were compared by referral route ("post hospitalisation", PH; "non-hospitalised", NH; and "post emergency department", PED). Symptoms associated with poor recovery or inability to return to work full-time were assessed using multivariable logistic regression. Findings1325 individuals were assessed (PH 547 [41.3%], PED 212 [16%], NH 566 [42.7%]. Compared with PH and PED groups, NH were younger (median 44.6 [35.6-52.8] vs 58.3 [47.0-67.7] and 48.5 [39.4-55.7] years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be from an ethnic minority (30.9%, 52.7% and 41.0%) and seen later after symptom onset (median [IQR]:194 [118-298], 69 [51-111] and 76 [55-128] days) (all p<0.0001). NH patients had similar rates of onward specialist referral as PH and PED groups (18.7%, 16.1% and 18.9%, p=0.452), and were more likely to require support for breathlessness (23.7%, 5.5% and 15.1%, p<0.001) and fatigue (17.8%, 4.8%, 8.0%, p<0.001). Hospitalised patients had higher rates of pulmonary emboli, persistent lung interstitial abnormalities, and other organ impairment. 716 (54.0%) individuals reported <75% of optimal health (median [IQR] 70% [55%-85%]). Overall, less than half of employed individuals felt able to return to work full-time at first assessment. InterpretationSymptoms following SARS-CoV-2 infection were significant in both post- and non-hospitalised patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required. FundingUCLH/UCL BRC Research in contextO_ST_ABSPrevious evidenceC_ST_ABSLong COVID and post-COVID syndrome were first identified in April 2020. We searched PubMed and medrxiv for articles published up to April 30th, 2021, using the keywords "long COVID", "post-COVID syndrome", "persistent symptoms", "hospitalised", "community" and "non-hospitalised". We identified 17 articles and 7 systematic reviews. Fifteen studies have considered symptoms, multi-organ or functional impairment but only one study to-date has considered all these variables in non-hospitalised COVID patients. No studies have compared symptom burden and management between non-hospitalised and hospitalised individuals as systematically assessed and managed in a dedicated post-COVID service. Added value of this studyFor the first time, we report the baseline characteristics, investigation and outcomes of initial assessment of all eligible patients in a dedicated multi-professional post-COVID service, including 547 post-hospitalisation, 566 non-hospitalised and 212 patients discharged from emergency department. Despite relatively low comorbidity and risk factor burden in non-hospitalised patients, we show that both non-hospitalised and hospitalised patients presenting with persistent symptoms after SARS-CoV2 infection have high rates of functional impairment, specialist referral and rehabilitation, even 6-12 months after the acute infection. These real-world data will inform models of care during and beyond the pandemic. Implications of all the available evidenceThe significant, long-lasting health and social consequences of SARS-CoV-2 infection are not confined to those who required hospitalisation. As with other long-term conditions, care of patients experiencing Long COVID or specific end-organ effects require consistent, integrated, patient-centred approaches to investigation and management. At public health and policy level, burden of post-COVID morbidity demands renewed focus on effective infection suppression for all age groups.
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The supply limitations of COVID-19 vaccines have led to the need to prioritize vaccine distribution. Obesity, diabetes and hypertension have been associated with an increased risk of severe COVID-19 infection. Approximately half as many individuals with a cardiovascular risk factor need to be vaccinated against COVID-19 to prevent related death as compared with individuals without a risk factor. Our analysis suggests that prioritizing adults with these cardiovascular risk factors for vaccination is likely to be an efficient way to reduce population COVID-19 mortality.
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BackgroundEthnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves. MethodsUsing data from the Office for National Statistics Public Health Data Asset on individuals aged 30-100 years living in private households, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and second wave (from 1st September to 28th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions. ResultsThe study population included over 28.9 million individuals aged 30-100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7 - 376.2] and 166.8 [141.7 - 191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4 - 390.1] and 127.1 [91.1 - 171.3] in men and women)background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves. ConclusionBetween the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes. *VN and NI contributed equally to this paper Research in contextO_ST_ABSEvidence before this studyC_ST_ABSA recent systematic review by Pan and colleagues demonstrated that people of ethnic minority background in the UK and the USA have been disproportionately affected by the Coronavirus (COVID-19) pandemic, compared to White populations. While several studies have investigated whether adjusting for socio-demographic and economic factors and medical history reduces the estimated difference in risk of mortality and hospitalisation, the reasons for the differences in the risk of experiencing harms from COVID-19 are still being explored during the course of the pandemic. Studies so far have analysed the ethnic differences in COVID-19 mortality in the first wave of the pandemic. The evidence on the temporal trend of ethnic inequalities in COVID-19 mortality, especially those from the second wave of the pandemic, is scarce. Added value of this studyUsing data from the Office for National Statistics (ONS) Public Health Data Asset on 29 million adults aged 30-100 years living in private households in England, we conducted an observational cohort study to examine the differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and second wave (from 1st September to 28th December 2020). We find that in the first wave all ethnic minority groups were at elevated risk of COVID-19 related death compared to the White British population. In the second wave, the differences in the risk of COVID-19 related death attenuated for Black African and Black Caribbean groups, remained substantially higher in people from Bangladeshi background, and worsened in people from Pakistani background. We also find that some of the factors explaining these differences in mortality have changed in the two waves. Implications of all the available evidenceThe risk of COVID-19 mortality during the first wave of the pandemic was elevated in people from ethnic minority background. An appreciable reduction in the difference in COVID-19 mortality in the second wave of the pandemic between people from Black ethnic background and people from the White British group is reassuring, but the continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy response. Focusing on treating underlying conditions, although important, may not be enough in reducing the inequalities in COVID-19 mortality. Focused public health policy as well as community mobilisation and participatory public health campaign involving community leaders may help reduce the existing and widening inequalities in COVID-19 mortality.
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ObjectivesThe epidemiology of post-COVID syndrome (PCS) is currently undefined. We quantified rates of organ-specific impairment following recovery from COVID-19 hospitalisation compared with those in a matched control group, and how the rate ratio (RR) varies by age, sex, and ethnicity. DesignObservational, retrospective, matched cohort study. SettingNHS hospitals in England. Participants47,780 individuals (mean age 65 years, 55% male) in hospital with COVID-19 and discharged alive by 31 August 2020, matched to controls on demographic and clinical characteristics. Outcome measuresRates of hospital readmission, all-cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney and liver diseases until 30 September 2020. ResultsMean follow-up time was 140 days for COVID-19 cases and 153 days for controls. 766 (95% confidence interval: 753 to 779) readmissions and 320 (312 to 328) deaths per 1,000 person-years were observed in COVID-19 cases, 3.5 (3.4 to 3.6) and 7.7 (7.2 to 8.3) times greater, respectively, than in controls. Rates of respiratory, diabetes and cardiovascular events were also significantly elevated in COVID-19 cases, at 770 (758 to 783), 127 (122 to 132) and 126 (121 to 131) events per 1,000 person-years, respectively. RRs were greater for individuals aged <70 than [≥] 70 years, and in ethnic minority groups than the White population, with the biggest differences observed for respiratory disease: 10.5 [9.7 to 11.4] for <70 years versus 4.6 [4.3 to 4.8] for [≥] 70 years, and 11.4 (9.8 to 13.3) for Non-White versus 5.2 (5.0 to 5.5) for White. ConclusionsIndividuals discharged from hospital following COVID-19 face elevated rates of multi-organ dysfunction compared with background levels, and the increase in risk is neither confined to the elderly nor uniform across ethnicities. The diagnosis, treatment and prevention of PCS require integrated rather than organ- or disease-specific approaches. Urgent research is required to establish risk factors for PCS.
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BackgroundEthnic minorities have experienced disproportionate COVID-19 mortality rates. We estimated associations between household composition and COVID-19 mortality in older adults ([≥] 65 years) using a newly linked census-based dataset, and investigated whether living in a multi-generational household explained some of the elevated COVID-19 mortality amongst ethnic minority groups. MethodsUsing retrospective data from the 2011 Census linked to Hospital Episode Statistics (2017-2019) and death registration data (up to 27th July 2020), we followed adults aged 65 years or over living in private households in England from 2 March 2020 until 27 July 2020 (n=10,078,568). We estimated hazard ratios (HRs) for COVID-19 death for people living in a multi-generational household compared with people living with another older adult, adjusting for geographical factors, socio-economic characteristics and pre-pandemic health. We conducted a causal mediation analysis to estimate the proportion of ethnic inequalities explained by living in a multi-generational household. ResultsLiving in a multi-generational household was associated with an increased risk of COVID-19 death. After adjusting for confounding factors, the HRs for living in a multi-generational household with dependent children were 1.13 [95% confidence interval 1.01-1.27] and 1.17 [1.01-1.35] for older males and females. The HRs for living in a multi-generational household without dependent children were 1.03 [0.97 - 1.09] for older males and 1.22 [1.12 - 1.32] for older females. Living in a multi-generational household explained between 10% and 15% of the elevated risk of COVID-19 death among older females from South Asian background, but very little for South Asian males or people in other ethnic minority groups. ConclusionOlder adults living with younger people are at increased risk of COVID-19 mortality, and this is a notable contributing factor to the excess risk experienced by older South Asian females compared to White females. Relevant public health interventions should be directed at communities where such multi-generational households are highly prevalent. FundingThis research was funded by the Office for National Statistics.
